Researchers say they have witnessed an unprecedented type of replication in organic robots created in the laboratory using seed cells. The results may, among other things, have an impact on regenerative medicine.
The discovery involves a xenobot – a simple, “programmable” organism created by assembling stem cells in a petri dish – and is described by a team of researchers from Tufts University, Harvard University and the University of Vermont in a paper published this week in Proceedings of the National Academy of Sciences.
“You can think of this as using the different cells [as] building blocks that you would build with LEGO or with Minecraft, “Douglas Blackiston, a co-author of the study, told NPR.
The researchers hope that one day – described by the same team in a paper published almost two years ago – these xenobots could be programmed to perform useful functions such as finding cancer cells in the human body or capturing harmful microplastics in the ocean.
The xenobots are made from cells taken from the African cleaved seed, el Xenopus laevis. The cells are not genetically modified at all, but simply combined in various arrangements to produce xenobots, says Blackiston, a senior researcher at the Allen Discovery Center at Tufts University and the Wyss Institute for Biologically Inspired Engineering at Harvard University.
The xenobots operate themselves using small hair-like structures known as the cilia. They tend to spin in a corkscrew way, which “turns out to be pretty good at assembling piles of things,” such as other cells, Blackiston says.
So the team used an artificial intelligence-driven computer simulation to see how they could manipulate xenobots into shapes that would be even better at picking things up.
An improved design provided an unexpected discovery
To that end, the original spherical shape of the xenobots is “not the best design,” Blackiston explains. Instead, the computer suggested a C-shape that looked like a snow plow or, as some have observed, Pac-Man. That form, he says, is extremely effective at assembling and assembling loose stem cells, which so naturally form large piles.
But when xenobots swept loose seed stem cells up into the dish, the researchers observed something remarkable: the piles of cells formed copies of the original xenobots.
Various forms of both sexual and asexual reproduction are, of course, well known in biology.
But what xenobots did – called kinematic self-replication – is new in living organisms, says Michael Levin, a professor of biology at Tufts and an associate faculty member at the Wyss Institute. It happens at the molecular level, but “we are not aware of any organism that reproduces or replicates in this way,” he says.
It takes about five days to make a copy under optimal conditions, the researchers say. The “offspring” does not assume the C-shaped body type of the parent generation, but returns to the less efficient, original spherical shape.
Xenobots are collections of living cells and have no brain or digestive system. But in a real sense, they can be programmed – to capture other cells, as in this study, or eventually to do other things. That’s why scientists think of them as tiny organic robots.
“The distinction between a robot and an organism is not nearly as sharp as … we used to think it was,” Levin told NPR. “These creatures, they have characteristics of both.”
In fact, the idea of kinematic self-replication is not entirely new – it was first proposed in the late 1940s by the mathematician John von Neumann. He envisioned machines that could choose between basic robot parts to produce copies of themselves, explains Sam Kreigman, a postdoc fellow at the Wyss Institute and lead author of the paper.
“We’ve had a lot of people who’ve been trying to make von Neumann machines out of robot parts for a long time, and there’s been limited success,” says Kreigman.
“We found that if you just relax the assumption that the robot should be made of metal and printed circuit boards and electronics, and instead use living cells, then von Neumann machines are actually quite easy to make,” he says to NPR.
Some scientists have ethical concerns
But that worries some scientists. Nita Farahany, a professor at Duke University in law and philosophy, studies ethics involved in new technologies and was not part of xenobot research. “Every time we try to take advantage of life … [we should] recognizing its potential to go really bad, “she told Smithsonian Magazine.
However, researchers note that, like a hypothetical von Neumann machine, a xenobot cannot copy itself without raw materials. As a result, there is virtually no chance that they could escape the lab and start reproducing on their own. The only thing the researchers have to do is remove the stock of loose stem cells, and there is nothing left to make new xenobots from.
And since no genetic material comes from the parent xenobot, they also cannot mutate or develop on their own, Blackiston says.
“It would be like finding loose parts of a human being that just hover around and stick them together to make a copy,” he says. “So it’s hard to figure out how [evolutionary] selection would act on it because nothing is passed on between each generation – each one is independent. “
What the researchers hope is that these xenobots and their ability to replicate themselves could one day be exploited for the benefit of humanity.
“This is really a first step, but you could think downward,” Blackiston says. “If we could program these better, they might be able to selectively capture and move specific cell types that we want, or help us shape something that we build in a regenerative medicine bowl.”
For Kreigman, it is interesting that “this kind of replication happens spontaneously.” Of course, it requires very specific conditions, he says, but “it did not have to be developed over billions of years,” he says.
“We think about how long it took for life to evolve on Earth,” Kreigman says. “It’s a very long story, but here in a dish under the right conditions, we found a whole new form of replication in organisms.”
And the discovery of a new form of self-replication, he says, shows that “perhaps life is more expected than unexpected.”
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